The purpose of this study is to investigate the relationship between arachidonate metabolism and immunological function in alveolar macrophages and peripheral blood monocytes from patients with non-small cell lung cancer. This is based on an appreciation for the impact that malgnant disease has on the function of macrophages and the manner in which that can be related to the alteration of cellular arachidonate metabolism. The expectation is that this study will provide fundamental information concerning this relationship with macrophages obtained from different sites including sites in proximity to tumor tissues. Comparisons will be made with macrophages obtained from patients with different histologies and different stages of primary lung cancer as well as patients with other solid tumor malignancies which are metastatic to the lung. In addition, comparisons will be made with marcophages obtained from different control groups including patients with inflammatory lung diseases or normal lungs. The functional assessments include i) spontaneous and inducible cytotoxic function, ii) spontaneous and inducible cytokine production, iii) spontaneous and inducible chemiluminescene response, and iv) accessory cell function for lymphokine activated killer cell induction. These tests would be performed in the presence of inhibitors of the cyclooxygenase pathway, the lipoxygenase pathway, or both pathways to assess the importance of arachidonate metabolism for these functions. Also, metabolic studies will be performed by reverse phase high pressure liquid chromatography (HPLC) to determine the effect of malignant disease on metabolism. The information obtained will be used to investigate ways in which the response of macrophages obtained from different sites, to biological activators such as gamma-inerferon (IFN), might be potentiated through the pharmacological manipulation of arachidonate metabolism. In addition, fundamental information relating to the impact of malignant disease on peripheral blood and alveolar macrophage function is expected to be gained.
